This is an investigator-initiated collaborative Phase II treatment study in which we will examine the hypothesis that treatment of patients with systemic lupus erythematosus (SLE) and active lupus nephritis with a blocking anti-human complement C5 monoclonal antibody will lead to objective improvement in renal disease parameters. The anti-C5 monoclonal antibody will lead to objective improvement in renal disease parameters. The anti-G5 monoclonal antibody will be provided by Alexion Pharmaceuticals. Several lines of investigation have supported the concept that C5 plays a central role in renal injury in antibody- mediated diseases such as SLE. While short term studies using a similar inhibitor have shown efficacy in patients with inflammatory complications of coronary artery bypass surgery, the proposed study represents the first application of this therapeutic strategy, chronic inhibition of complement C5 activation, to patients with autoimmune diseases. Patients enrolled in this double blinded, placebo controlled Phase II study will be those who have active but clinically stable nephritis and, thus, do not require immediate introduction of high dose cyclophosphamide or other cytotoxic drug therapy. Two patient groups, treated and untreated (vehicle control only as a placebo), will be studied. The primary outcome variable will be proteinuria. Secondary outcomes will include other measures of renal disease activity, other measures of lupus activity and measure of complement activation. Three Specific Aims will be pursued. Specific Aim #1. Determine the changes in renal disease activity that accompany short term treatment with an anti-C5 monoclonal antibody in patients with active lupus nephritis. Specific Aim #2. Identify changes in levels of complement activation fragments that accompany treatment with anti-c5 monoclonal antibody in patients with active lupus nephritis. Specific Aim #3. Assess these patients treated with an inhibitory anti-C5 monoclonal antibody for evidence of toxicity. This study is integrated into other components and goals of the Denver Autoimmunity Center itself in several ways. First, it utilizes a population of patients drawn from several sources in the Denver Autoimmunity Center. Second, it meets the goal of extending the use of complement inhibitors from animal models, which are being extensively studied here in the laboratory of the P.I. and others, into clinical trials in patients. Third, the analysis of the role of complement inhibitors as compared to cytokine inhibitors is a major component of the Basic Science Project #2 headed by Dr. William P. Arend.